GB1142484A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

1,142,484. Steroids. UPJOHN CO. 23 March, 1966 [24 March, 1965], No. 12857/66. Heading C2U. [Also in Division A5] The invention comprises compounds of the formulµ wherein R, R 1 and R 2 each represent hydrogen or methyl, W is in which R 3 is hydrogen or the acyl radical of a C 1 -C 16 hydrocarbon carboxylic acid, R 4 is hydrogen or C 1 -C 4 hydrocarbon radical, X is Y is hydrogen or fluorine; and Z is compounds of the formulµ and the corresponding 17-keto compounds wherein R, R 1 , R 2 and R 3 are as defined above, compounds of the formulµ and a process that comprises treating a 6α-(2<SP>1</SP>- hydroxyethyl)-androst-4-ene-3-one with a sulphonic acid halide and subjecting the 6α-(2<SP>1</SP>- sulphonyloxyethyl)-androst-4-en-3-one so obtained to treatment with a strong base to produce the corresponding spiro-[androst-4-ene-6, 1<SP>1</SP>-cyclopropane]-3-one. If desired the 17#- hydroxy compounds may be acylated to form the 17#-acylates, the 3-keto compounds subjected to reduction to form the 3#-hydroxy compounds, the 11# hydroxy compound oxidized to form the corresponding 11-keto compounds and/or acylation may be effected to produce the corresponding 3#-acylate, 17#- acylate or 3#,17#-diacylate. Ring A saturation may be effected with hydrogen and palladized charcoal, and reduction of the 3-keto group with alkali metal borohydride. Oxidation may be effected with chromic acid, an N- haloamide or N-haloimide. The 3-tetrahydropyranyl ethers are obtained by treating a 3- hydroxy-17-acyloxy compound with dihydropyran in the presence of a Lewis acid and then if desired hydrolysing to produce the 17- hydroxy compound which in turn may be oxidized to form a 17-keto compound. The latter products may be hydrolysed in 3-position and the 3(3-hydroxy compounds so produced oxidized to the corresponding 3-keto compounds. The 17α - alkyl - 17# - hydroxy compounds are obtained by treating the corresponding 17-keto compounds with a Grignard reagent and if desired may be acylated to form the corresponding 17a-alkyl-17#-acyloxy compounds. #<SP>1</SP>'<SP>4</SP>-compounds are obtained from the corresponding #<SP>4</SP>-compounds by dehydrogenation, e.g. by fermentation or chemically as with Se02. The 2-hydroxymethylene products are obtained from the 2-unsubstituted compounds by treatment with an alkyl formate and sodium hydride in an inert atmosphere and if desired are treated with a lower alkanol in the presence of an acidic agent to give the corresponding 2-alkoxymethylene derivative.